Abstract
Soft matter can serve as a template to guide the growth of inorganic components with well-controlled structural features. However, the limited design space of conventional organic and biomolecular templates restricts the complexity and accuracy of templated growth. In past decades, the blossoming of structural DNA nanotechnology has provided us with a large reservoir of delicate-framework nucleic acids with design precision down to a single base. Here, we describe a DNA origami silicification (DOS) approach for generating complex silica composite nanomaterials. By utilizing modified silica sol–gel chemistry, pre-hydrolyzed silica precursor clusters can be uniformly coated onto the surface of DNA frameworks; thus, user-defined DNA–silica hybrid materials with ~3-nm precision can be achieved. More importantly, this method is applicable to various 1D, 2D and 3D DNA frameworks that range from 10 to >1,000 nm. Compared to pure DNA scaffolds, a tenfold increase in the Young’s modulus (E modulus) of these composites was observed, owing to their soft inner core and solid silica shell. We further demonstrate the use of solidified DNA frameworks to create 3D metal plasmonic devices. This protocol provides a platform for synthesizing inorganic materials with unprecedented complexity and tailored structural properties. The whole protocol takes ~10 d to complete.
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Data availability
All data generated or analyzed during this study are included in the paper and its Supplementary Information and are available from the corresponding author on request.
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Acknowledgements
This project was supported by the National Science Foundation of China (grant nos. 21390414, 21329501, 21603262 and 21675167), the National Key R&D Program of China (grant nos. 2016YFA0201200 and 2016YFA0400900) and the Key Research Program of Frontier Sciences, CAS (grant no. QYZDJ-SSW-SLH031). L.W., C.F. and H.Y. thank the National Key R&D Program of China (grant no. 2016YFA0400900). H.Y. and F.Z. thank the US National Science Foundation, the Office of Naval Research, the Army Research Office, the National Institutes of Health and the Department of Energy for financial support.
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Contributions
C.F. and H.Y. supervised the research. X.L., C.F. and H.Y. conceived the research and designed the experiments. F.Z. designed the DNA nanostructures. X.J. and X.L. carried out silicification experiments and characterization. M.P. and X.D. analyzed the EM and AFM data. X.J., F.Z., M.P., X.D., J.L., L.W., X.L., C.F. and H.Y. interpreted data and wrote the manuscript.
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Peer review information: Nature Protocols thanks Haitao Liu, Jussi Toppari and other anonymous reviewer(s) for their contribution to the peer review of this work.
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Liu, X. et al. Nature 559, 593–598 (2018): https://www.nature.com/articles/s41586-018-0332-7
Integrated supplementary information
Supplementary Figure 1 Capture design of DNA origami AuNRs hybrids.
a, left, Capture site on tetrahedron DNA origami. right, sequences of capture strands and corresponding complementary strands on AuNRs. b. detailed capture site in staples. The capture strands are extending from 5’ of staples site. The sites are designed in the middle of yellow strands in images to make sure the directions of captures strands are towards outside. To keep the broken staples not too short (>20 bases), we stick the short staples after breaking with the closer staples (sequences table: M1-M9).
Supplementary Figure 2 Gel electrophoresis of different DNA frames.
S1: P8064; a: tetrahedron-100 nm; b: cube; S2: M13mp18; c: triangle; d: rectangle; e: cross; f: 6-helix; g: hemisphere; h: toroid; i: ellipsoid; S3: phiX174 DNA; j: diatom; M1:50 bp DNA ladder; k: tetrahedron-16 nm; Blue box is drawn to highlight the target band. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 3 AFM and TEM characterization of different DNA frames.
a and d, design of DNA frames. b and e, AFM images of DNA frames (left, zoom-out; right, zoom-in). c and f, TEM images of DNA frames (left, zoom-out; right, zoom-in). Scale bars, zoomed in, 50 nm, and zoomed out, 250 nm. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 4 TEM characterization of synthetic AuNRs, ssDNA-modified AuNRs and assembled DNA origami AuNRs hybrids.
a, TEM characterization of synthetic AuNRs. b, TEM characterization of ssDNA modified AuNRs. The images showed the AuNRs are modified with a thin layered ssDNA (after negatively stained). c, after mixing tetrahedron DNA origami with complementary ssDNA strands modified AuNRs, DNA origami AuNRs hybrids can be made. The whole structures are collapsed due to its flexibility. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 5 The influence of TMAPS concentrations and ratios between TMAPS and TEOS (TEOS was 2.0%) on DOS triangle.
Reaction time was 24 h. Lower than 2.0% or higher than 2.5% TMAPS induced incomplete reactions. The reason for the former situation was that the lower concentration could not compete with the Mg2+, which then induced an incomplete reaction between the TMAPS and DNA. The reason for the latter situation arose possibly because of excess free TMAPS provided free nucleation sites in the solution. Scale bars, 200 nm. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 6 The influence of TEOS concentrations (TMAPS was 2.0% (wt/wt)) on DOS triangle.
Reaction time was 24 h. As the concentration of the TEOS increased, the DOS was more and more obvious before a 2.0% TEOS concentration was achieved. Then, the DOS did not change much between a 2.0% and 6.0% concentration of TEOS. Different sized spherical silica (no more than 100 nm) were produced after a 7.0% TEOS concentration due to self-aggregation of the TMAPS molecules and the heterogeneous silicification. Scale bars, 200 nm. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 7 Geometrically precise control of DOS structures.
a, A user-specified DOS nanopore with the smallest diameter down to sub-10 nanometer. From left to right panel: design, AFM images for pure DNA origami, class averaged TEM images, and size distribution of silica nanopore measured from raw TEM images, respectively. Histograms of three different pore sizes were normalized and fitted to Gaussian distribution curves (light blue), and the red dashes indicated direct measurements of the pore sizes from class averaged TEM images. b, DOS-diatom nanostructures. From left to right panel: the design model of a DNA origami template, AFM images before and after silicification, and the averaged TEM image of a DOS-diatom nanostructure, respectively. Scale bars, 50 nm. All unmarked units refer to nm. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 8 AFM images of DOS triangle and corresponding height diagrams at different silicification periods.
a, b. The blue line represents the height of the triangle DNA origami. The corresponding statistical data were shown in Fig. 3c. Scale bars, 100 nm. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 9 AFM images show the integrity of triangle DNA-origami framework and DOS triangle, that was reacted for 1, 2 and 5 d, under increasing applied forces.
The heights of the sample decreased dramatically, judging from the height of the scale bar. When the applied forces surpassed 3,000 pN, the DNA framework was almost destroyed. The strengths of all of the DOS triangles were enhanced and were stronger than the DNA framework. Also, the integrity of the DOS triangles were obviously increased with longer silicification time. Scale bars, 100 nm. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 10 Destructive AFM tip forces on the integrity statistics of a blank DNA origami and a DOS nanostructure that was reacted for 1 and 5 d.
Based on the E-modulus data, it was expected that the compression strength of the DOS nanostructures would be greatly enhanced. We applied increasing AFM tip forces to test the mechanical property of both the pure DNA origami and the triangular shaped DOS. The derived E-modulus agreed well with the AFM data for the sample integrities under different setoff forces. The pure DNA origami structures were heavily damaged under 1,600 pN. With larger forces up to 3,000 pN, the height signal was not stable and thus could not be used with the rest of the statistical results. On the contrary, the DOS with 5 days of growth was almost intact even under 3,000 pN. The DOS with 1 day of growth was gradually destroyed as the force increased from 150 pN to 3,000 pN. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 11 AFM images show the DMT modulus of triangle DNA-origami framework and DOS triangle, that was reacted for 1, 2 and 5 d, under increasing applied forces.
The modulus of the sample and the mica increased dramatically when the force was increased, judging from the changes in the color of the images. This phenomenon indicated that the modulus was directly measured by the AFM peaking force QNM and that using the DMT modulus was not accurate. We noticed, while using the same force at a different point in time that the modulus of the sample increased slightly. The colors of the sample were becoming lighter with a longer silicification time. However, the colors of the DNA-origami sample were changing quickly, maybe because the DNA sample was being squashed by the tip when the force was higher than 800 pN. This phenomenon demonstrated the enhanced rigidity of the DOS triangle. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 12 Nanomechanical studies on DOS nanostructures.
a, Young’s Modulus (E-modulus) derived from force curves, using a membrane substrate effect correction (MSEC) model. The E-modulus of a DOS triangle after 5 days’ silicification was about 10 times greater than the original DNA nanostructure. b, Comparison between a DMT model and a MSEC model. δmax /height indicates that the maximum indentation depth was divided by sample thickness, E / Esample indicates the dispersion of the E-modulus when taking substrate effects into consideration. The E-modulus data that was deducted from the MSEC model was thickness and forces independent. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 13 AFM zoomed out/in images of the 5-d DOS tetrahedron under 1.0 nN.
a. The zoomed out images showed homogeneous well-formed DOS tetrahedrons on the mica surface. b. Section diagrams showed that the DOS tetrahedrons had standing edges that were almost completely straight. Along with the TEM results, the above data proved that the structural strength of DNA framework had been enhanced. Scale bars, 50 nm. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 14 Exemplary mechanical libraries of tough, yet flexible DOS tetrahedrons.
Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary Figure 15 Surface roughness (as evaluated by the arithmetic average of the absolute values, Ra) of typical 2D DOS structures.
a. A graph of the time and setoff force dependent Ra value of a DOS triangle. For the 1 Day sample, the Ra values were positively correlated to the setoff forces, because the DOS triangle was partially damaged under higher forces. For the 5 Day sample, the Ra values were negatively correlated to the setoff forces. The Ra value varied from ~0.3 nm to ~0.7 nm. b. The Ra values of typical 2D DOS structures were collected at 200–400 pN. Because the images were not taken with a single tip, the datasets showed semi-quantitative results. The Ra values varied in the range from ~0.4 nm to ~0.7 nm, which indicated that the roughness corresponded with the one- or two-layer difference in the silica tetrahedron since the bond length of Si - O is 166 pm. c. Corresponding selected data area for roughness statistics. Scale bars, 100 nm. Nature. 2018. Vol. 559, 593–598. Copyright Nature Publishing Group.
Supplementary information
Supplementary Information
Supplementary Figures 1–15 and Supplementary Tables 1–4
Supplementary Data 1
The tutorial files for calculation of the E modulus derived from force curves, using an MSEC model.
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Jing, X., Zhang, F., Pan, M. et al. Solidifying framework nucleic acids with silica. Nat Protoc 14, 2416–2436 (2019). https://doi.org/10.1038/s41596-019-0184-0
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DOI: https://doi.org/10.1038/s41596-019-0184-0
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